Ataka Takuya, Kimura Noriyuki, Kaneko Naoki, Masuda Teruaki, Takeuchi Yosuke, Yabuuchi Kenichi, Mizukami Takeshi, Takeuchi Tsukasa, Ito Temmei, Tasai Hideaki, Miyagawa Takehiko, Hanai Shunya, Iwamoto Shinichi, Matsubara Etsuro
Department of Neurology Faculty of Medicine Oita University Oita Japan.
Koichi Tanaka Mass Spectrometry Research Laboratory Shimadzu Corporation Kyoto Japan.
Alzheimers Dement (N Y). 2024 Oct 10;10(4):e70008. doi: 10.1002/trc2.70008. eCollection 2024 Oct-Dec.
Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).
This prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan‒Meier curves.
The participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0-80.0] years). Plasma biomarkers correlated with cortical amyloid uptake ( = 0.667-0.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein ε4 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84, < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline ( = -0.575, < 0.001).
Plasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.
Plasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.
既往研究已在临床队列中检验了血浆淀粉样蛋白β（Aβ）生物标志物的预测准确性。然而，它们在基于社区的队列中预测淀粉样蛋白阳性患者的准确性尚不清楚。本研究旨在确定Aβ前体蛋白669 - 711/Aβ1 - 42、Aβ1 - 40/1 - 42及其复合生物标志物对社区居住的轻度认知障碍（MCI）老年人脑淀粉样蛋白沉积或临床进展的预测准确性。
本前瞻性队列研究于2015年8月至2019年9月进行。随后，参与者在研究开始后长达8年的时间里接受了随访认知评估。在基线时从年龄≥65岁的MCI老年人中采集血样。使用免疫沉淀 - 质谱法分析血浆Aβ生物标志物。使用受试者工作特征曲线分析评估血浆生物标志物对脑淀粉样蛋白状态的准确性。使用多元线性回归分析检查合并症与血浆Aβ标志物之间的关系。使用Kaplan - Meier曲线评估血浆生物标志物与向阿尔茨海默病（AD）痴呆临床转化的关联。
参与者包括107例患者（57例[53.3%]为女性，中位年龄：76.0[72.0 - 80.0]岁）。血浆生物标志物与皮质淀粉样蛋白摄取相关（= 0.667 - 0.754）。复合生物标志物在预测淀粉样蛋白阳性方面具有最佳曲线下面积（0.943，95%置信区间[CI]：0.901至0.985）。载脂蛋白ε4状态与血浆淀粉样蛋白生物标志物水平升高显著相关。基线时复合生物标志物水平高的参与者转化为AD痴呆的风险更大（风险比10.74，95%CI：3.51至32.84，<0.001）。较高的复合生物标志物与更快的认知衰退速度相关（= -0.575，<0.001）。
血浆Aβ复合生物标志物可作为基于社区的队列中淀粉样蛋白沉积的替代指标和疾病进展的预测指标。
血浆淀粉样蛋白β（Aβ）生物标志物与11C - 匹兹堡化合物B摄取相关，主要在额叶/顶颞叶皮质和后扣带回。淀粉样蛋白复合生物标志物在基于社区的轻度认知障碍队列中能够以0.943的高曲线下面积预测淀粉样蛋白正电子发射断层扫描阳性。基线时较高的淀粉样蛋白复合生物标志物与简易精神状态检查评分恶化以及8年内发生阿尔茨海默病（AD）痴呆的高风险显著相关。淀粉样蛋白复合生物标志物能够以0.860的高曲线下面积预测向AD痴呆的临床进展。载脂蛋白Eε4状态影响血浆Aβ生物标志物水平。
